Klebsiella pneumoniae invasive syndrome with liver, lung, and brain abscesses complicated with pulmonary fungal infection: a case report and review of the literature.

BACKGROUND: Klebsiella pneumoniae invasion syndrome (KPIS) is a severe multi-site infection that is usually caused by hypervirulent Klebsiella pneumoniae. The bacteria are relatively common in Asian diabetics and can cause organ abscesses or sepsis. When patients develop intracranial infection, the prognosis is poor. After anti-infective treatment, the Klebsiella pneumoniae-induced liver and lung abscesses and pulmonary fungal infection were relieved, but the brain abscesses worsened. Such complex and severe infection cases are rarely reported. Early identification of intracranial infection, selection of antibiotics with high concentrations in cerebrospinal fluid, and active treatment of complications such as diabetes and fungal infection are of great significance for the prognosis of patients. CASE PRESENTATION: A 71-year-old patient diagnosed with liver abscess in another hospital was transferred to our hospital due to a worsening condition. On day 1 (day of admission), the patient was given invasive mechanical ventilation, continuous renal replacement therapy combined with endotoxin adsorption, antimicrobial treatment with imipenem-cilastatin, and percutaneous catheter drainage for liver abscess. Metagenomic next-generation sequencing in bronchoalveolar lavage fluid indicated Klebsiella pneumoniae (K. pneumoniae), Candida albicans, and Aspergillus flavus complex, and no viruses were detected. Blood and pus cultures revealed K. pneumoniae that was sensitive to piperacillin/tazobactam. The anti-infection therapy was adjusted to piperacillin/tazobactam combined with voriconazole. On day 14, a head computed tomography (CT) scan showed no significant changes, and a chest CT scan showed absorption of multiple abscesses in both lungs. The patient was still unconscious. After the endotracheal tube was removed, cranial magnetic resonance imaging (MRI) showed multiple brain abscesses. Finally, his family gave up, and the patient was discharged and died in a local hospital. CONCLUSION: In cases of K. pneumoniae infection, the possibility of intracranial, liver, lung, or other site infections should be considered, and physicians should be vigilant for the occurrence of KPIS. For patients suspected of developing an intracranial infection, cerebrospinal fluid should be tested and cultured as soon as possible, a head MRI should be performed, and antibiotics with high distribution in cerebrospinal fluid should be used early. When patients are complicated with diabetes, in addition to glycemic control, vigilance for concurrent fungal infections is also needed.

Effects of music therapy on pain relief during fundus screening in infants: Randomized controlled clinical trial.

BACKGROUND: To determine the efficacy of music therapy on pain relief during fundus screening in infants. METHODS: The sample consisted of infants aged 0 to 3 months who required fundus screening. Infants were randomized to fast music, slow music, and control groups. All groups underwent fundus screening under topical anesthesia. Music therapy was provided to the music groups prior to, during, and after the operation. The patient's heart rate (HR), transcutaneous oxygen saturation, and crying decibel were measured. The Face, Legs, Activity, Cry, Consolability scale was used for pain measurement. RESULTS: A total of 300 subjects' data were collected. The quantitative analysis revealed that in both music groups, peripheral capillary oxygen saturation and satisfaction levels increased while pain scores decreased (P < .05). The slow music group's HR was shown to have significantly decreased (P < .05). CONCLUSION: Music therapy can effectively reduce pain and crying, and increase blood oxygen saturation during fundus examination of infants. Music with a rhythm of 60 to 80 beats per minute can decrease HR. Music therapy must be remembered to increase infants' comfort during fundus examination.

Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic Adenovirus.

Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.

Self-assembled short peptides: Recent advances and strategies for potential pharmaceutical applications.

Self-assembled short peptides have intrigued scientists due to the convenience of synthesis, good biocompatibility, low toxicity, inherent biodegradability and fast response to change in the physiological environment. Therefore, it is necessary to present a comprehensive summary of the recent advances in the last decade regarding the construction, route of administration and application of self-assembled short peptides based on the knowledge on their unique and specific ability of self-assembly. Herein, we firstly explored the molecular mechanisms of self-assembly of short peptides, such as non-modified amino acids, as well as Fmoc-modified, N-functionalized, and C-functionalized peptides. Next, cell penetration, fusion, and peptide targeting in peptide-based drug delivery were characterized. Then, the common administration routes and the potential pharmaceutical applications (drug delivery, antibacterial activity, stabilizers, imaging agents, and applications in bioengineering) of peptide drugs were respectively summarized. Last but not least, some general conclusions and future perspectives in the relevant fields were briefly listed. Although with certain challenges, great opportunities are offered by self-assembled short peptides to the fascinating area of drug development.

Oncolytic Virus-Driven Biotherapies from Bench to Bedside.

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies.

Novel immune-risk score of gastric cancer: A molecular prediction model combining the value of immune-risk status and chemosensitivity.

Gastric cancer is still one of the most common and deadly malignancies in the world. Not all patients could benefit from chemotherapy or chemoradiotherapy due to tumor heterogeneity. Therefore, identifying different subgroups of patients is an important trend for obtaining more effective responses. However, few molecular classifications associated with chemosensitivity are based on immune-risk status. In this study, we obtained six key immune-related genes. Using these genes, we constructed a molecular model related to immune-risk status and calculated an individual immune-risk score. The score showed great efficiency and stability in predicting prognosis and identifying different subgroups where persons could benefit from postoperative adjuvant therapy. The patients could be divided into different risk groups based on the immune-related score. For patients in the low-risk group, both postoperative chemoradiotherapy and chemotherapy could significantly improve prognosis on overall survival (OS) and disease-free survival (DFS) (DFS, P < 0.001 and P = 0.041, respectively; OS, P < 0.001, P = 0.006, respectively) and chemoradiotherapy was significantly superior than simple chemotherapy (DFS, P = 0.031; OS, P = 0.027). For patients with an intermediate-risk score, postoperative chemoradiotherapy showed a statistically significant survival advantage over no anticancer treatment (P = 0.004 and P = 0.002, respectively), while chemotherapy did not. Compared with no adjuvant treatment, neither postoperative chemoradiotherapy nor chemotherapy made significant difference for patients in the high-risk group. Combining the value of immune-risk status and chemosensitivity, the immune-risk score could not only offer us prognostic evaluation and adjuvant treatment guidance, but also improve our understanding about the binding point between chemotherapy or chemoradiotherapy and the immune system, which may be helpful for further expanding the application of immunotherapy.

Bone mesenchymal stem cells transplantation combined with mild hypothermia improves the prognosis of cerebral ischemia in rats.

Bone marrow mesenchymal stem cells (BMSCs) are used as a great promising choice for the treatment of cerebral ischemia. Herein, we discuss the neuroprotective effects of the combination of BMSCs transplantation and mild hypothermia (MH) in an ischemia-reperfusion rat model. First, BMSCs were isolated using density gradient centrifugation and the adherent screening method, followed by culture, identification and labeling with DAPI. Second, adult male SD rats were divided into 5 groups: sham group (surgery without blockage of middle cerebral artery), model group (middle cerebral artery occlusion (MCAO) was established 2h prior to reperfusion), BMSCs group (injection of BMSCs via the lateral ventricle 24h after MCAO), MH group (mild hypothermia for 3h immediately after MCAO) and combination therapy group (combination of BMSCs and MH). Finally, the modified neurological severity score (mNSS) test was performed to assess behavioral function at different time points (before MCAO, before transplantation, at day 1, day 5 and day 10 after transplantation). After that, the brain was subjected to TTC staining, and the homing and angiogenesis were evaluated by immumofluorescence and immunohistochemistry. Immunofluorescence staining and Western Blot analysis were performed to calculate the percentage of the infarct area and explore glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF). Our results showed that the combination therapy significantly decreased mNSS scores (P<0.01) and reduced the percentage of the infarct area (P<0.01) than a single treatment. Moreover, the expression of GFAP and VEGF increased significantly in the combination therapy group (at day 5, day 10 after transplantation; at all time points after transplantation, respectively) compared to the single treatment groups. Taken together, it was suggested that the combination of BMSCs transplantation and MH can significantly reduce the percentage of the infarct area and improve functional recovery by promoting homing and angiogenesis, which may be a beneficial treatment for cerebral ischemia.

Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer­associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC and adjacent normal tissues were identified, followed by pathway enrichment analysis of DEGs. Next, the protein­protein interaction (PPI) network of DEGs was built and visualized. Analyses of modules in the PPI network were then performed to identify the functional core genes. Finally, survival analysis of core genes was conducted. A total of 256 genes were identified as DEGs between the GC samples and normal samples, including 169 downregulated and 87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the present study identified a total of 143 GO terms and 21 pathways. Six clusters of functional modules were identified, and the genes associated with these modules were screened out as the functional core genes. Certain core genes, including collagen type 12 α1 chain (COL12A1), glutathione S­transferase α3 (GSTA3), fibrinogen α chain (FGA) and fibrinogen γ chain (FGG), were the first reported to be associated with GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4x10­6), FGA (P=0.00075) and FGG (P=1.4x10­5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.

Development of a risk-scoring system to evaluate the serosal invasion for macroscopic serosal invasion positive gastric cancer patients.

BACKGROUND: The status of serosal invasion is often discordance between pathological and intraoperative evaluation. Our study sought to develop a risk-scoring system (RSS) to predict the probability of pT4a for macroscopic serosal invasion (MSI) positive patients and reevaluate the serosal invasion status. PATIENTS AND METHODS: A total of 1301 pT3/pT4a gastric cancer patients with curative surgery were reviewed. We constructed the RSS to predict the probability of pT4a and assigned MSI-positive patients into different risk groups based on the risk scores. The prognostic significance of these risk groups was also evaluated. RESULTS: Univariate and multivariate analyses identified that tumor location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI-positive patients in high-risk group had similar survival with pT4a patients. We incorporated these two groups into one stage and proposed a novel revised-T stage. Two-step multivariate analyses indicated that the revised-T stage showed better prediction ability for prognosis and peritoneal recurrence assessment than original pT stage and MSI status. CONCLUSIONS: In our present study, we developed a RSS to predict the probability of pT4a for MSI-positive patients. Based on our RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI-positive patients in clinical practice. Future studies should include other preoperative predictors to improve the clinical utility of our model.

GRIK3: A novel oncogenic protein related to tumor TNM stage, lymph node metastasis, and poor prognosis of GC.

Glutamate receptor, ionotropic, kainate 3 (GRIK3), as a member of the glutamate kainate receptor family, mainly participated in neuroactive ligand receptor interaction pathway. Other members of GRIK family were previously reported to regulate cellular migration, transformation, and proliferation in tumor. However, the mechanism of GRIK3 in tumor is still unclear. Therefore, the purpose of our study was to reveal the expression and clinical significance of GRIK3 in gastric cancer (GC). First, we performed the expression analysis and survival analysis of GRIK3 using The Cancer Genome Atlas (TCGA) database, and the results showed that the GRIK3 expressed differentially between gastric cancer tissues and the adjacent normal tissues and that higher expression of GRIK3 was associated with poor survival outcomes. And the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that GRIK3 mainly took part in cancer-related process. Subsequently, the validated immunohistochemistry showed that GRIK3 expressed higher in the GC tissues than in the matched normal tissues and the patients with overexpressed GRIK3 had worse survival outcomes. The univariate and multivariate analyses suggested that the expression of GRIK3 was an independent prognostic factor to predict GC prognosis. Furthermore, additional experiment showed that the lymph node metastasis tissues had higher GRIK3 expression than their matched primary GC tissues. These findings suggested that elevated GRIK3 expression could serve as an independent prognostic biomarker and a novel potential treatment target for patients with GC.

Rare upper gastrointestinal hemorrhage of cetuximab: A case report.

RATIONALE: cetuximab, an epidermal growth factor receptor inhibitor, is a targeted therapeutic regimen of colorectal cancers. Several common adverse effects have been found, such as cutaneous or gastrointestinal toxicity. However, according to the articles had been published, upper gastrointestinal bleeding (UGIB) is considered to be rare and its mechanism remains unclear. PATIENT CONCERNS: In this report, we presented a 42-year-old male patient with advanced recto-sigmoid cancer. After palliative operation, the patient suffered from complete upper gastrointestinal (GI) obstruction, which was induced by extensive abdominal metastasis of the tumor. Considering his poor condition, we chose the targeted drug, cetuximab, as his further treatment. But after the application of cetuximab, the UGIB immediately happened twice in this patient. DIAGNOSIS: UGIB, as a rare complication of cetuximab, occured to the patient. INTERVENTIONS: We stopped the bleeding with thrombin, hemocoagulase and somatostatin and suspended the subsequent treatment plan of cetuximab. At the same time, anti-shock treatment was given immediately. OUTCOMES: He was died of respiratory and circulatory failure caused by UGIB and advanced tumor eventually. LESSONS: UGIB should be considered as a rare but severe complication of cetuximab. When cetuximab is applied for patients with advanced colon tumors, more cautions should be required if the patients are accompanied by upper gastrointestinal obstruction. In addition, for those patients who suffered from UGIB recently, cetuximab should be prohibited if the Rockall score ranged > 5 points.